Pharmacological Identification of P2X1, P2X4 and P2X7 Nucleotide Receptors in the Smooth Muscles of Human Umbilical Cord and Chorionic Blood Vessels

Valdecantos, Pablo A.; Briones, René; Moya, Pablo R.; Germaín, A; Huidobro‐Toro, J. Pablo

doi:10.1053/plac.2002.0862

Cited by 33 publications

(53 citation statements)

References 30 publications

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“…2). Our RT-PCR data indicated that P2X7 subunit mRNA is not expressed in HGOA VSMCs, although these subunits have been suggested to be expressed in human placenta VSMCs [34]. However, we found no detectable immunofluorescence for P2X7 subunits in HGOA VSMCs (data not shown).…”

Section: P2x Receptor Gene and Protein Expressionmentioning

confidence: 53%

Vascular smooth muscle cells from small human omental arteries express P2X1 and P2X4 receptor subunits

Nichols

Povstyan

Albert

et al. 2014

Purinergic Signalling

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Stimulation of P2X receptors by ATP in vascular smooth muscle cells (VSMCs) is proposed to mediate vascular tone. However, understanding of P2X receptor-mediated actions in human blood vessels is limited, and therefore, the current work investigates the role of P2X receptors in freshly isolated small human gastro-omental arteries (HGOAs). Expression of P2X1 and P2X4 receptor subunit messenger RNA (mRNA) and protein was identified in individual HGOA VSMCs using RT-PCR and immunofluorescent analysis and using Western blot in multi-cellular preparations. ATP of 10 μmol/l and αβ-meATP of 10 μmol/l, a selective P2X receptor agonist, evoked robust increases in [Ca 2+ ] i in fluo-3-loaded HGOA VSMCs. Pre-incubation with 1 μmol/l NF279, a selective P2X receptor antagonist, reduced the amplitude of αβ-meATP-induced increase in [Ca 2+ ] i by about 70 %. ATP of 10 μmol/l and αβ-meATP of 10 μmol/l produced similar contractile responses in segments of HGOA, and these contractions were greatly reduced by 2 μmol/l NF449, a selective P2X receptor inhibitor. These data suggest that VSMCs from HGOA express P2X1 and P2X4 receptor subunits with homomeric P2X1 receptors likely serving as the predominant target for extracellular ATP.

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Section: P2x Receptor Gene and Protein Expressionmentioning

confidence: 53%

Vascular smooth muscle cells from small human omental arteries express P2X1 and P2X4 receptor subunits

Nichols

Povstyan

Albert

et al. 2014

Purinergic Signalling

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“…The role of the AA cascade in the generation of potent and efficacious vasoactive metabolites is of paramount importance for the maintenance of the vasomotor tone of human placental vessels (72)(73)(74). We demonstrated that prostaglandin E 2 or F 2␣ (35) and even adenosine contracts main conductance placental vessel rings, probably by the release of thromboxane (74), reiterating the importance of AA metabolites in the regulation of placental vasomotor tone. AA has been shown to activate protein kinase C, which in turn phosphorylates the MLCP regulator CIP17 (75).…”

Section: Discussionmentioning

confidence: 83%

“…Full-term placentas were transported to the laboratory within 5-15 min of childbirth; immediately thereafter, segments of superficial HCA were carefully dissected from the main body to perform the protocols. For some experiments, segments conserved an intact endothelium, whereas in other experiments, the vessel segments were manually denuded of the endothelial cell layer by gently rubbing the internal vessel surface with a cotton swab; this procedure was described to eliminate the internal endothelial layer without damaging the adjacent smooth muscle layer (35). To perform other protocols, as will be specified separately, HCA vessel segments were perfused with one of the nucleotide receptor agonists for 1, 2, or 4 min; immediately thereafter, these vessel segments were placed in liquid nitrogen until further tissue processing.…”

Section: Methodsmentioning

confidence: 99%

UTP Controls Cell Surface Distribution and Vasomotor Activity of the Human P2Y2 Receptor through an Epidermal Growth Factor Receptor-transregulated Mechanism

Norambuena

Palma

Poblete

et al. 2010

Journal of Biological Chemistry

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Extracellular nucleotides transmit signals into the cells through the P2 family of cell surface receptors. These receptors are amply expressed in human blood vessels and participate in vascular tone control; however, their signaling mechanisms remain unknown. Here we show that in smooth muscle cells of isolated human chorionic arteries, the activation of the P2Y 2 receptor (P2Y 2 R) induces not only its partition into membrane rafts but also its rapid internalization. Cholesterol depletion with methyl-␤-cyclodextrin reduced the association of the agonist-activated receptor into membrane rafts but did not affect either the UTPmediated vasoconstrictions or the vasomotor responses elicited by both serotonin and KCl. Ex vivo perfusion of human chorionic artery segments with 1-10 M UTP, a selective P2Y 2 R agonist, displaced the P2Y 2 R localization into membrane rafts within 1 min, a process preceded by the activation of both RhoA and Rac1 GTPases. AG1478, a selective and potent inhibitor of the epidermal growth factor receptor tyrosine kinase activity, not only blocked the UTP-induced vasomotor activity but also abrogated both RhoA and Rac1 activation, the P2Y 2 R association with membrane rafts, and its internalization. Altogether, these results show for the first time that the plasma membrane distribution of the P2Y 2 R is transregulated by the epidermal growth factor receptor, revealing an unsuspected functional interplay that controls both the membrane distribution and the vasomotor activity of the P2Y 2 R in intact human blood vessels.

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“…mRNA for P2Y 4 , P2Y 6 and P2Y 11 receptors was also found. P2X1, P2X4 and P2X7 receptors were also present on the smooth muscle of human chorionic blood vessels [408].…”

Section: Placentamentioning

confidence: 89%

Purinergic signalling in the reproductive system in health and disease

Burnstock

2013

Purinergic Signalling

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There are multiple roles for purinergic signalling in both male and female reproductive organs. ATP, released as a cotransmitter with noradrenaline from sympathetic nerves, contracts smooth muscle via P2X1 receptors in vas deferens, seminal vesicles, prostate and uterus, as well as in blood vessels. Male infertility occurs in P2X1 receptor knockout mice. Both short-and long-term trophic purinergic signalling occurs in reproductive organs. Purinergic signalling is involved in hormone secretion, penile erection, sperm motility and capacitation, and mucous production. Changes in purinoceptor expression occur in pathophysiological conditions, including pre-eclampsia, cancer and pain.

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Pharmacological Identification of P2X1, P2X4 and P2X7 Nucleotide Receptors in the Smooth Muscles of Human Umbilical Cord and Chorionic Blood Vessels

Cited by 33 publications

References 30 publications

Vascular smooth muscle cells from small human omental arteries express P2X1 and P2X4 receptor subunits

Vascular smooth muscle cells from small human omental arteries express P2X1 and P2X4 receptor subunits

UTP Controls Cell Surface Distribution and Vasomotor Activity of the Human P2Y2 Receptor through an Epidermal Growth Factor Receptor-transregulated Mechanism

Purinergic signalling in the reproductive system in health and disease

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